Transcription factors (TFs) play a vital role in the regulation of gene expression thereby making them critical to many cellular processes. In this study, we used graph machine learning methods to create a compendium of TF cascades using data extracted from the STRING database. A TF cascade is a sequence of TFs that regulate each other, forming a directed path in the TF network. We constructed a knowledge graph of 81,488 unique TF cascades, with the longest cascade consisting of 62 TFs. Our results highlight the complex and intricate nature of TF interactions, where multiple TFs work together to regulate gene expression. We also identified 10 TFs with the highest regulatory influence based on centrality measurements, providing valuable information for researchers interested in studying specific TFs. Furthermore, our pathway enrichment analysis revealed significant enrichment of various pathways and functional categories, including those involved in cancer and other diseases, as well as those involved in development, differentiation, and cell signaling. The enriched pathways identified in this study may have potential as targets for therapeutic intervention in diseases associated with dysregulation of transcription factors. We have released the dataset, knowledge graph, and graphML methods for the TF cascades, and created a website to display the results, which can be accessed by researchers interested in using this dataset. Our study provides a valuable resource for understanding the complex network of interactions between TFs and their regulatory roles in cellular processes.

The intra- and inter-species genetic diversity of bacteria and the absence of 'reference', or the most representative, sequences of individual species present a significant challenge for sequence-based identification. The aims of this study were to determine the utility, and compare the performance of several clustering and classification algorithms to identify the species of 364 sequences of 16S rRNA gene with a defined species in GenBank, and 110 sequences of 16S rRNA gene with no defined species, all within the genus Nocardia. A total of 364 16S rRNA gene sequences of Nocardia species were studied. In addition, 110 16S rRNA gene sequences assigned only to the Nocardia genus level at the time of submission to GenBank were used for machine learning classification experiments. Different clustering algorithms were compared with a novel algorithm or the linear mapping (LM) of the distance matrix. Principal Components Analysis was used for the dimensionality reduction and visualization. Results: The LM algorithm achieved the highest performance and classified the set of 364 16S rRNA sequences into 80 clusters, the majority of which (83.52%) corresponded with the original species. The most representative 16S rRNA sequences for individual Nocardia species have been identified as 'centroids' in respective clusters from which the distances to all other sequences were minimized; 110 16S rRNA gene sequences with identifications recorded only at the genus level were classified using machine learning methods. Simple kNN machine learning demonstrated the highest performance and classified Nocardia species sequences with an accuracy of 92.7% and a mean frequency of 0.578.

Background: Comparative genomics has put additional demands on the assessment of similarity between sequences and their clustering as means for classification. However, defining the optimal number of clusters, cluster density and boundaries for sets of potentially related sequences of genes with variable degrees of polymorphism remains a significant challenge. The aim of this study was to develop a method that would identify the cluster centroids and the optimal number of clusters for a given sensitivity level and could work equally well for the different sequence datasets. Results: A novel method that combines the linear mapping hash function and multiple sequence alignment (MSA) was developed. This method takes advantage of the already sorted by similarity sequences from the MSA output, and identifies the optimal number of clusters, clusters cut-offs, and clusters centroids that can represent reference gene vouchers for the different species. The linear mapping hash function can map an already ordered by similarity distance matrix to indices to reveal gaps in the values around which the optimal cut-offs of the different clusters can be identified. The method was evaluated using sets of closely related (16S rRNA gene sequences of Nocardia species) and highly variable (VP1 genomic region of Enterovirus 71) sequences and outperformed existing unsupervised machine learning clustering methods and dimensionality reduction methods. This method does not require prior knowledge of the number of clusters or the distance between clusters, handles clusters of different sizes and shapes, and scales linearly with the dataset. Conclusions: The combination of MSA with the linear mapping hash function is a computationally efficient way of gene sequence clustering and can be a valuable tool for the assessment of similarity, clustering of different microbial genomes, identifying reference sequences, and for the study of evolution of bacteria and viruses.

With the onset of diffusion-based generative models and their ability to generate text-conditioned images, content generation has received a massive invigoration. Recently, these models have been shown to provide useful guidance for the generation of 3D graphics assets. However, existing work in text-conditioned 3D generation faces fundamental constraints: (i) inability to generate detailed, multi-object scenes, (ii) inability to textually control multi-object configurations, and (iii) physically realistic scene composition. In this work, we propose CG3D, a method for compositionally generating scalable 3D assets that resolves these constraints. We find that explicit Gaussian radiance fields, parameterized to allow for compositions of objects, possess the capability to enable semantically and physically consistent scenes. By utilizing a guidance framework built around this explicit representation, we show state of the art results, capable of even exceeding the guiding diffusion model in terms of object combinations and physics accuracy.

We introduce SODA, a self-supervised diffusion model, designed for representation learning. The model incorporates an image encoder, which distills a source view into a compact representation, that, in turn, guides the generation of related novel views. We show that by imposing a tight bottleneck between the encoder and a denoising decoder, and leveraging novel view synthesis as a self-supervised objective, we can turn diffusion models into strong representation learners, capable of capturing visual semantics in an unsupervised manner. To the best of our knowledge, SODA is the first diffusion model to succeed at ImageNet linear-probe classification, and, at the same time, it accomplishes reconstruction, editing and synthesis tasks across a wide range of datasets. Further investigation reveals the disentangled nature of its emergent latent space, that serves as an effective interface to control and manipulate the model's produced images. All in all, we aim to shed light on the exciting and promising potential of diffusion models, not only for image generation, but also for learning rich and robust representations.

Stochastic simulation models, while effective in capturing the dynamics of complex systems, are often too slow to run for real-time decision-making. Metamodeling techniques are widely used to learn the relationship between a summary statistic of the outputs (e.g., the mean or quantile) and the inputs of the simulator, so that it can be used in real time. However, this methodology requires the knowledge of an appropriate summary statistic in advance, making it inflexible for many practical situations. In this paper, we propose a new metamodeling concept, called generative metamodeling, which aims to construct a "fast simulator of the simulator". This technique can generate random outputs substantially faster than the original simulation model, while retaining an approximately equal conditional distribution given the same inputs. Once constructed, a generative metamodel can instantaneously generate a large amount of random outputs as soon as the inputs are specified, thereby facilitating the immediate computation of any summary statistic for real-time decision-making. Furthermore, we propose a new algorithm -- quantile-regression-based generative metamodeling (QRGMM) -- and study its convergence and rate of convergence. Extensive numerical experiments are conducted to investigate the empirical performance of QRGMM, compare it with other state-of-the-art generative algorithms, and demonstrate its usefulness in practical real-time decision-making.

Recent studies attempted to utilize multilayer perceptrons (MLPs) to solve semisupervised node classification on graphs, by training a student MLP by knowledge distillation from a teacher graph neural network (GNN). While previous studies have focused mostly on training the student MLP by matching the output probability distributions between the teacher and student models during distillation, it has not been systematically studied how to inject the structural information in an explicit and interpretable manner. Inspired by GNNs that separate feature transformation $T$ and propagation $\Pi$, we re-frame the distillation process as making the student MLP learn both $T$ and $\Pi$. Although this can be achieved by applying the inverse propagation $\Pi^{-1}$ before distillation from the teacher, it still comes with a high computational cost from large matrix multiplications during training. To solve this problem, we propose Propagate & Distill (P&D), which propagates the output of the teacher before distillation, which can be interpreted as an approximate process of the inverse propagation. We demonstrate that P&D can readily improve the performance of the student MLP.

In this paper, we introduce a novel swarm application, swarm synergy, where robots in a swarm intend to form communities. Each robot is considered to make independent decisions without any communication capability (silent agent). The proposed algorithm is based on parameters local to individual robots. Engaging scenarios are studied where the silent robots form communities without the preset conditions on the number of communities, community size, goal location of each community, and specific members in the community. Our approach allows silent robots to achieve this self-organized swarm behavior using only sensory inputs from the environment. The algorithm facilitates the formation of multiple swarm communities at arbitrary locations with unspecified goal locations. We further infer the behavior of swarm synergy to ensure the anonymity/untraceability of both robots and communities. The robots intend to form a community by sensing the neighbors, creating synergy in a bounded environment. The time to achieve synergy depends on the environment boundary and the onboard sensor's field of view. Compared to the state-of-art with similar objectives, the proposed communication-free swarm synergy shows comparative time to synergize with untraceability features.

Feature selection is critical in machine learning to reduce dimensionality and improve model accuracy and efficiency. The exponential growth in feature space dimensionality for modern datasets directly results in ambiguous samples and redundant features, which can severely degrade classification accuracy. Quantum machine learning offers potential advantages for addressing this challenge. In this paper, we propose a novel method, quantum support vector machine feature selection (QSVMF), integrating quantum support vector machines with multi-objective genetic algorithm. QSVMF optimizes multiple simultaneous objectives: maximizing classification accuracy, minimizing selected features and quantum circuit costs, and reducing feature covariance. We apply QSVMF for feature selection on a breast cancer dataset, comparing the performance of QSVMF against classical approaches with the selected features. Experimental results show that QSVMF achieves superior performance. Furthermore, The Pareto front solutions of QSVMF enable analysis of accuracy versus feature set size trade-offs, identifying extremely sparse yet accurate feature subsets. We contextualize the biological relevance of the selected features in terms of known breast cancer biomarkers. This work highlights the potential of quantum-based feature selection to enhance machine learning efficiency and performance on complex real-world data.

We investigate the molecular gene expressions studies and public databases for disease modelling using Probabilistic Graphical Models and Bayesian Inference. A case study on Spinal Muscle Atrophy Genome-Wide Association Study results is modelled and analyzed. The genes up and down-regulated in two stages of the disease development are linked to prior knowledge published in the public domain and co-expressions network is created and analyzed. The Molecular Pathways triggered by these genes are identified. The Bayesian inference posteriors distributions are estimated using a variational analytical algorithm and a Markov chain Monte Carlo sampling algorithm. Assumptions, limitations and possible future work are concluded.